For example, IGFBP3 itself has a proapoptotic function, whereas IGFBP5 has a significant influence on bone mineral density (BMD) acquisition and maintenance in a gender- and age-dependent fashion, which may have implications for the gender-biased progression of osteoporosis.(55) Our results have demonstrated that IGFBP3 and IGFBP4, but not IGFBP5, can antagonize IGF-2 action on BMP-9-induced osteogenic differentiation. This evidence concerns the gene GDF2 and osteoporosis.